Temporal specification of blood progenitors from mouse embryonic stem cells and induced pluripotent stem cells

被引:57
作者
Irion, Stefan [1 ]
Clarke, Raedun L. [1 ]
Luche, Herve [2 ]
Kim, Injune [3 ]
Morrison, Sean J. [4 ,5 ]
Fehling, Hans-Joerg [6 ]
Keller, Gordon M. [1 ]
机构
[1] Univ Hlth Network, McEwen Ctr Regenerat Med, Toronto, ON M5G 1L7, Canada
[2] Univ Mediterranee, Ctr Immunol Marseille Luminy, INSERM CNRS, Marseille 09, France
[3] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea
[4] Univ Michigan, Howard Hughes Med Inst, Inst Life Sci, Dept Internal Med, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA
[6] Univ Clin Ulm, Inst Immunol, Lab Mol Immunol, D-89081 Ulm, Germany
来源
DEVELOPMENT | 2010年 / 137卷 / 17期
基金
美国国家卫生研究院;
关键词
AGM; Hematopoiesis; Induced pluripotent stem cell; Embryonic stem cells; Sox17; Yolk sac; Mouse; YOLK-SAC; PRIMITIVE STREAK; DEFINITIVE HEMATOPOIESIS; DEVELOPMENTAL PATHWAY; AORTIC ENDOTHELIUM; NERVOUS-SYSTEM; STROMAL CELLS; IN-VITRO; GENERATION; DIFFERENTIATION;
D O I
10.1242/dev.042119
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The efficient and reproducible generation of differentiated progenitors from pluripotent stem cells requires the recapitulation of appropriate developmental stages and pathways. Here, we have used the combination of activin A, BMP4 and VEGF under serum-free conditions to induce hematopoietic differentiation from both embryonic and induced pluripotent stem cells, with the aim of modeling the primary sites of embryonic hematopoiesis. We identified two distinct Flk1-positive hematopoietic populations that can be isolated based on temporal patterns of emergence. The earliest arising population displays characteristics of yolk sac hematopoiesis, whereas a late developing Flk1-positive population appears to reflect the para-aortic splanchnopleura hematopoietic program, as it has reduced primitive erythroid capacity and substantially enhanced myeloid and lymphoid potential compared with the earlier wave. These differences between the two populations are accompanied by differences in the expression of Sox17 and Hoxb4, as well as in the cell surface markers AA4.1 and CD41. Together, these findings support the interpretation that the two populations are representative of the early sites of mammalian hematopoiesis.
引用
收藏
页码:2829 / 2839
页数:11
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